Center investigators are studying numerous genes and their protein products in the brain's reward circuits to define their role in the regulation of mood and motivation under normal circumstances and in animal models of depression and antidepressant action. To accomplish this goal, the Behavioral Core has established an extremely broad battery of behavioral tests in rats and mice. This battery includes routine measures of locomotor activity and anxiety-like behavior,, as well as several standard depression-related tests such as the forced swim and learned helplessness tests. The battery also incorporates several additional assays that provide complementary information about an animal's affective state;these include measures of sexual behavior, incentive motivation for food, intracranial self-stimulation, social interaction, and sophisticated cognitive tasks, to name some examples. In addition, Core personnel continually work to extend this battery to additional tests. For example, we recently adapted the social defeat paradigm, where certain behavioral abnormalities respond to chronic (but not acute) antidepressant treatment, to study stress-induced neuroadaptations in mouse brain. The imperative to employ such a large battery of behavioral tests is that it is difficult to infer something about complex behavior from a single test or even a limited number of tests. Rather, by utilizing numerous complementary measures we are able to infer, with much greater accuracy, the role of a given gene in complex behavior related to depression. By consolidating these behavioral tests within a centralized Core, we can ensure rigorous control over the data as well as facilitate comparisons and contrasts of experimental results from the individual Projects. This consolidation also makes financial sense, since we can concentrate and maximize efficient use of our behavioral expertise. The role of specific molecular targets in behavioral responses related to mood and motivation are tested with a variety of approaches, including advanced mouse mutagenesis and viral gene transfer in conjunction with the Transgenic Core. The Behavioral Core then provides routine, relatively high throughput behavioral tests for investigators in the Center's preclinical Projects (1-4). Encouraging findings are pursued with more sophisticated behavioral tests also via this Core. In addition, the Core obtains routine neuroendocrine measurements (e.g., plasma corticosterone levels) and antidepressant blood levels in behaving animals as needed for particular experiments.
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